Homolycorine type alkaloids

An interesting study of homolycorine type alkaloids with a saturated ring C has been made by Jeff and coworkers (208). They describe empirical correlations of A/-methyl chemical shifts with stereochemical assignments of the B/C and C/D ring junction. 

The alkaloids of the homolycorine series, formed by a restructuring of lycorine-type alkaloids, are absent from some tribes of the Amaryllidaceae, such as the Amaryllideae or Hemantheae (44). For that reason, the presence of these alkaloids is a distinctive feature of the Narcisseae tribe. Moreover, all the Narcissus alkaloids of the homolycorine series display a B/C ring junction with a cis stereochemistry. An exceptional homolycorine-type alkaloid is dubiusine (33), which has an unusual hydroxybutyryl substituent (72). 

Figure 7. Conversion of norpluviine (12) to homolycorine-type alkaloids.

The conversion of norpluviine 261 into homolycorine 3 has been validated via the benzylic oxidation at C6 position followed by B-ring opening to form an amino aldehyde with a free hydroxyl group, which gives alkaloid lycorenine 54 after 77,0-methylation [112]. Finally, a subsequent oxidation produces homolycorine 3 (Scheme 17.5). Recently, the transformation from lycorine-type skeleton into homolycorine-type alkaloid has been experimentally demonstrated through a total synthesis of alkaloid clivonine 76 [113]. 

Lycorenine-type alkaloids derived from [2]benzopyrano [3,4g]indole) including both lycorenine and homolycorine ... 

The pyrrolo[de]phenanthridine alkaloids (lycorine type) and the 2-benzopirano-[3,4-g]indole alkaloids (homolycorine type) both originate from an ortho-para phenol-oxidative coupling (Fig. 5). 

H NMR spectroscopy gives important information about the different types of Amaryllidaceae alkaloids. Several early contributions about homolycorine and crinane-haemanthamine type alkaloids were made by Hawksworth et al. (206) and Haugwitz et al. (207). In the last decade, the routine use of 2D NMR tecniques (COSY, NOESY, ROESY, etc.) has facilitated the structural assignments and the settling of their stereochemistry. A compilation of the different H NMR spectra, arranged according to the different skeleton types is shown in Table 4. 

NMR data of Homolycorine type compounds lactone alkaloids. 

These alkaloids are among the most abundant of the bases derived from the [2]benzopyrano[3,4gf]indole nucleus in the Amaryllidaceae family, and the title of this section is derived from this fact. Lycorenine (LXVI) was one of the first Amaryllidaceae alkaloids to be studied and a summary of the chemical degradations leading to this structure (without stereochemical implications) has been given in Volumes II and VI. Lycorenine and the corresponding lactone, homolycorine (LXVII), not only serve as the reference alkaloids of the group for recent spectroscopic studies but also provides a chemical correlation with the lycorine-type alkaloids. Several important chemical interconversions are given below. 

The alkaloids of the lycorine and homolycorine groups are, on the whole, the most common alkaloids in this genus. Lycorine (1), galanthine (7), and pluviine (11) (lycorine type) and homolycorine (26) and lycorenine (35) (homolycorine type) are particularly frequent, lycorine being the most abundant. The presence of these alkaloids is very significant in the sections Narcissus (mainly lycorine type). Pseudonarcissi (mainly homolycorine type), and Tazettae of the wild species, and in the Divisions 1, 2, and 4 of cultivars. 

It is well established that profiles of alkaloids vary with time, location, and developmental stage. In many instances, the site of biosynthesis is restricted to a single organ, but accumulation of the corresponding products can be detected in several other plant tissues. Long-distance transport must take place in these instances. There are only a few data on the ontogenic variations and distribution of alkaloids in species of the Amaryllidaceae family, and some results have been obtained in Narcissus species, such as N. assoanus (with only lycorine-type alkaloids) or N. confusus (with alkaloids of the homolycorine, hemanthamine, tazettine, and galanthamine types) 84,87). 

The biological conversion of protocatechuic aldehyde into lycorenine (35), which proceeds via (9-methylnorbelladine (87) and norpluviine (12), first involves a reduction of the aldehyde carbonyl, and afterward, in the generation of lycorenine (35), oxidation of this same carbon atom. The absolute stereochemistry of these processes has been elucidated in subsequent experiments (194), and the results show that hydrogen addition and removal take place on the re-face of the molecules concerned (195), the initially introdueed hydrogen being the one later removed (196). It is noteworthy that norpluviine (12), unlike pluviine (11), is converted in Narcissus King Alfred primarily to alkaloids of the homolycorine type. Benzylie... 

NMR Data of Homolycorine-Type Compounds Lactone Alkaloids. 

On the basis of recent phytochemistry investigation about Amaryllidaceae alkaloids, anew 12-type classificatimi, including (1) norbelladine type, (2) lycorine type, (3) homolycorine type, (4) crinine and haemanthamine types, (5) tazettine type, (6) montanine type, (7) pUcamine type, (8) graciline type, (9) galanthindole type, (10) galanthamine type, (11) phenanthridone and phenanthridine types, and (12) other minor species populations, are deduced according to their ring systems. Representative structures for each type of Amaryllidaceae alkaloids are shown in Tables 17.2-17.13. 

Alkaloids of this series encompass all bases derived from the [2]benzo-pyrano[3,4gr]indole nucleus. Although homolycorine and lycorenine are moderately abundant, most of the alkaloids of this type occur either in very minor amounts in accessible plants or in large quantities in species that are difficult to obtain. 

The large number of structurally diverse Amaryllidaceae alkaloids are classified mainly into nine skeleton types, for which the representative alkaloids are norbelladine, lycorine, homolycorine, crinine, hemanthamine, narciclasine, tazettine, montanine, and galanthamine (Fig. 1). With the aim of unifying the numbering system of the different skeleton types, Ghosal s model will be used in this review (20). 

Skeleton types LY, lycorine FIL, homolycorine HT, hemanthamine TZ, tazettine NC, narcielasine MN, montanine GA, galanthamine OA, other alkaloids. Alkaloid names see Tables I-VII. 

Synthesis of alkaloids of the first structural type [such as lycorine (8), norpluviine (9), lycorenine (10), and homolycorine (11)] in various daffodil varieties may occur as indicated (Fig. 33.4). Radioactively labeled norbellidine (5) is incorporated into norpluviine (9). 

---